The present invention relates to reaction wells and more particularly to devices incorporating arrays of microtitre reaction wells.
Microtitre plates provide convenient handling systems for processing, shipping, and storing small liquid samples. Such devices are especially useful in high-throughput screening and combinatorial chemistry applications and are well suited for use with robotic automation systems which are adapted to selectively deliver various substances into different individual wells of the microtitre plate. As such, microtitre plates have proven especially useful in various biological, pharmacological, and related processes which analyze and/or synthesize large numbers of small liquid samples.
Standard multi-well microtitre plates come in a range of sizes, with shallow well plates having well volumes on the order of 200 to 300 microliters and deep well plates typically having well volumes of 1.2 mL or 2.0 mL. A common example of a multi-well microtitre plate system is the standard 96-well microplate. Such microplates are typically fabricated from a variety of materials including polystyrene, polycarbonate, polypropylene, PTFE, glass, ceramics, and quartz.
Unfortunately, standard microtitre plates suffer from a number of limitations, particularly with regard to chemical synthesis. For example, spillage, leakage, evaporation loss, airborne contamination of well contents, and inter-well cross-contamination of liquid samples are some of the common deficiencies that limit the application of standard microtitre plate assemblies in high through-put synthesis systems.
Existing multi-well reaction arrays are large, bulky devices which can not be conveniently mounted to, and removably exchanged between, devices which handle standard microtitre plates such as centrifuges, orbital shakers, shelf dryers, analytical injectors and liquid-handling robots. In addition, another disadvantage of existing multi-well reaction arrays is that convenient temperature control of the reaction wells is quite limited. Presently, temperature control is typically accomplished by way of large, bulky heating and cooling blocks which can not conveniently be used on liquid-handling robots.
The present invention provides a reaction well array device in a microtitre plate format which is adapted to substantially eliminate cross-contamination, spillage, and evaporation from the individual reaction wells. Moreover, the present device is adapted to provide a sealed environment such that the contents in the interior of the reaction wells are not exposed to the external environment. An additional advantage of the present reaction well array device is that gas pressure can easily be equalized over the entire array of reaction wells. Another advantage of the present system is that gases can selectively be introduced and/or removed from the reaction environment without exposing the contents of the reaction wells to the external environment. Specifically, the present device is specifically adapted to selectively receive liquid samples introduced or removed by way of robotic or manually controlled injection needles, without violating the internal sealed reaction environment of the system.
The present invention also provides a base plate which can be attached for convenient mounting of the system on a variety of other devices which handle standard microtitre plate formats such as centrifuges, orbital shakers, shelf dryers, analytical injectors and liquid handling robots. In addition, the present invention also provides a small efficient temperature control system for adjusting and maintaining preferred temperatures in the reaction wells.
In one preferred embodiment, the present invention provides a microtitre reaction system having an array of reaction tubes or wells which are integrally formed into an underlying support rack. In an alternative preferred embodiment, the present invention provides an array of reaction wells which are each selectively removable from an underlying support rack. An advantage of this second embodiment is that each of the various reaction wells can be selectively removed and/or replaced in the support rack, as is desired. As such, the present microtitre device is readily adaptable for manual removal of individual reaction wells or for use with an automated robotic system for removing and replacing individual reaction wells.
A porous gas distribution plate is positioned over the array of reaction wells. In a preferred embodiment, the porous gas distribution plate has an array of holes passing therethrough with a single hole disposed over the open top end of each of the reaction wells. In a preferred embodiment, the porous gas distribution plate is formed of small polypropylene particles which are fused together with porous passages or channels remaining between the particles so as to permit gas diffusion through the plate. The porous gas diffusion plate operates to permit gas passage in a common area over the array of adjacent reaction wells.
A gasket and a top cover are positioned over the porous gas distribution plate such that a sealed reaction environment is provided for each of the various reaction wells in the array. A gas purge vent is preferably provided in the present device such that gases may be selectively introduced or removed from the reaction environment while liquid transfer out of any individual well or between any two adjacent wells is prevented.
The optional base plate can be attached to conveniently convert the support rack and reaction wells into a deep well microtitre plate configuration such that it can be mounted to a variety of different devices including, centrifuges, orbital shakers, shelf dryers, robotic liquid handlers and automated injectors for analytical and preparative chromatography and the like.
Moreover, the present invention may optionally include a small heating and cooling system which is attached thereto such that enhanced temperature control in the reaction environment is achieved.
Optionally, a generally funnel-shaped reactor cap is included and is received into the open top end of each reaction well, prior to the placement of the gas distribution plate thereover. An example of such generally funnel-shaped reactor caps can be found in U.S. patent application No. 08/953,441, assigned to Texperts, Inc., a Delaware Corporation. The advantages of such funnel-shaped reactor caps include their substantial inhibition of liquid passage out of each reaction well such that liquid spillage is substantially prevented for all orientations of the reaction well array. Such funnel-shaped reactor caps are typically held together in an array formation by way of an interlocking web. In such an array, the reactor caps can be easily fit into an array of reaction wells as a single unit.